What this Trial Is About

This research aims to better understand the effects of gene therapy using adeno-associated virus (AAV) in adult male patients with severe hemophilia A or B who have received gene transfer treatment. The study specifically focuses on patients who have more than 1% endogenous factor VIII or IX expression after gene therapy. Researchers want to learn whether the therapeutic protein expression is due to AAV DNA integrating into liver cells or maintained as separate DNA, and to study long-term changes in liver cells after gene transfer. Participants will undergo a liver biopsy procedure to collect up to three tissue samples. These samples will be analyzed to reveal how many liver cells have been affected by the gene therapy, changes in gene expression patterns, epigenetic changes over time, and the effects of the transgene on liver cells. The biopsies will be taken from patients who have received gene therapy in one of three specific clinical trials, occurring any time from one month to 15 years after their treatment. During the study, researchers will assess the biopsy samples using specialized sequencing to detect AAV integration in liver cells. The study will monitor patients' coagulation function and overall safety. This detailed analysis aims to provide important new information about the life cycle of AAV in humans and the safety and effectiveness of AAV gene therapy for hemophilia, benefiting those who have already had gene therapy and future patients considering this treatment.

Liver Biopsy In Haemophilia Gene Therapy